Case Presentation: A 52-year-old man with hypertension, type 2 diabetes (HbA1c 8%), BMI 17 presented with progressive dyspnea and orthopnea. Examination showed jugular venous distension, bibasilar crackles, and pitting edema. Laboratory studies revealed BNP >5000 pg/mL, and troponin 133 ng/L. Transthoracic echocardiography showed reduced left-ventricular systolic function (EF 40–45%) consistent with new HFrEF. Evaluation for renal injury identified nephrotic-range proteinuria. Chest CT revealed diffuse atraumatic fractures of varying age involving the vertebrae, ribs, clavicle, and manubrium, and a 2.5-cm right adrenal nodule (30 HU). A dexamethasone suppression test (DST) showed elevated morning cortisol (23 µg/dL) with undetectable aldosterone and normal metanephrines. Symptoms improved with IV diuresis and guideline-directed therapy. He was discharged with multidisciplinary follow-up, and outpatient testing reconfirmed cortisol excess (21.3 µg/dL). Nephrology attributed his proteinuria to secondary membranous nephropathy from cortisol excess, and orthopedics confirmed healed osteoporotic fractures. He began teriparatide and remains under endocrine and surgical follow up.
Discussion: Classic Cushingoid features occur in fewer than one-third of patients; many instead present with cardiometabolic disease. Evaluation for endocrine causes of metabolic diseases remains uncommon, contributing to delayed diagnosis. Cortisol excess can impair cardiac structure and function, and improvement in ejection fraction has been reported after biochemical cure. Occult cortisol excess can mimic primary cardiometabolic disease and obscure reversible etiology. Increasing detection of adrenal incidentalomas—present in up to 10% of adults over age 70—has revealed that 20–50% demonstrate mild autonomous cortisol secretion (MACS). Hypertension occurs in up to 87% of affected patients and diabetes in up to 74%, emphasizing that cardiometabolic disease often predominates overt Cushingoid stigmata. Despite this, evaluation for secondary endocrine causes remains rare; for example, screening for primary hyperaldosteronism occurs in < 2% of eligible hypertensive patients despite a prevalence of 5–10% overall and up to 35% in resistant hypertension. Cardiac dysfunction is a particularly underrecognized consequence of cortisol excess. Histopathology shows cardiomyocyte hypertrophy, myofibrillolysis, and interstitial fibrosis, mediated by mineralocorticoid receptor–driven sensitization to angiotensin II. Case reports describe improvement in left-ventricular ejection fraction—often by 10–15%—following correction of hypercortisolism, underscoring the potential for meaningful reversal. Early recognition of cortisol excess carries major therapeutic implications. Adrenalectomy improves or normalizes hypertension in two-thirds of patients and diabetes in more than half. Several case reports have demonstrated cardiac remodeling reversal with biochemical cure with early intervention.
Conclusions: This case reframes Cushing syndrome along a continuum of cortisol excess that intersects with common disease. Appreciating endocrine contributions to conditions such as heart failure, hypertension, and diabetes enables a shift from symptom management to true disease intervention. Heightened clinical vigilance for hypercortisolism—even without classic features—may offer a rare opportunity to reverse cardiometabolic decline.